Genome-wide gene expression analyses reveal unique cellular characteristics related to the amenability of HPC/HSCs into high-quality induced pluripotent stem cells

Background: Transcription factor-mediated reprogramming can efficiently convert differentiated cells into induced pluripotent stem cells (iPSCs). Furthermore, many cell types have been shown to be amenable to reprogramming into iPSCs, such as neural stem cells, hematopoietic progenitor and stem cells (HPC/HSCs). However, the mechanisms related to the amenability of these cell types to be reprogrammed are still unknown.

Methods: Herein, we attempt to elucidate the mechanisms of HPC/HSC reprogramming using the sequential reprogramming system that we have previously established.

Results: We found that HPC/HSCs were amenable to transcription factor-mediated reprogramming, which yielded a high frequency of fully reprogrammed HPC/HSC-iPSCs. Genome-wide gene expression analyses revealed select down-regulated tumor suppressor and mesenchymal genes as well as up-regulated oncogenes in HPC/HSCs compared with mouse embryonic fibroblasts (MEFs), indicating that these genes may play important roles during the reprogramming of HPC/HSCs. Additional studies provided insights into the contribution of select tumor suppressor genes (p21, Ink4a and Arf) and an epithelial-to-mesenchymal transition (EMT) factor (Snail1) to the reprogramming process of HPC/HSCs.

Conclusions: Our findings demonstrate that HPC/HSCs carry unique cellular characteristics, which determine the amenability of HPC/HSCs to be reprogrammed into high-quality iPSCs.